Conference Coverage

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

Involvement of the head, neck, face, and hands with atopic dermatitis was associated with a significantly higher impact on health-related quality of life and appeared to be associated with more severe AD, according to a large, cross-sectional study of patients with AD.

“While we know that head, neck, face, and hands seem to be significantly affected by patients with AD, there is a limited evidence basis regarding the prevalence and health-related quality of life impact of AD in these areas,” presenting author Lawrence F. Eichenfield, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium.

For the study, Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues evaluated 533 patients from the TARGET-DERM AD cohort, an ongoing, longitudinal, observational study launched in 2019 that captures patients with AD in 44 community or academic sites in the United States.

Adult, adolescent, and pediatric patients with moderate or severe Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores at enrollment were included in the analysis. The researchers used the Patient-Oriented Scoring AD (PO-SCORAD) index to gather information on involvement of the head, neck, face, hands, or other areas, and the Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index/Children’s DLQI (CDLQI) to measure health-related quality of life outcomes.

Of the 533 study participants, 453 (85%) had AD affecting the head, neck, face, hands, and other areas, while 80 (15%) had AD located in other body regions not including the head, neck, face, or hands. About 38% of all patients were using systemic treatments; most were using topical treatments.

Comorbid immune system disorders (including allergic and hypersensitivity disorders) were noted in 44.8% of patients, infections in 32.5%, asthma in 26.5%, hypertension in 18.6%, depression in 15.8%, and anxiety in 12.4%, with similar proportions observed in those with or without head, neck, face, and hand involvement.

However, patients with head, face, neck, and hand involvement, when compared with patients without those affected areas, were more likely to have severe vIGA scores (28.5% vs. 16.3%, P = .02) and a higher median total body surface area affected (15% vs. 10%, P ≤ .01). Also, while bivariable analyses did not detect statistical differences in POEM and DLQI/CDLQI by body region involvement, multivariable-adjusted models showed that patients with head, neck, face, and hand involvement were more than twice as likely to report higher DLQI/CDLQI (odds ratio, 2.09) and POEM (OR, 2.51) scores than those without head, face, neck, and hand involvement.

“These findings highlight the importance of detailed assessment of specific areas affected by AD to personalize treatment approaches to the needs of patients,” Dr. Eichenfield concluded.

Raj Chovatiya MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that the findings confirm clinical suspicions about the unique and heightened impact of facial, head/neck, and hand dermatitis. “These data show that a detailed skin examination is necessary for a complete assessment of AD,” he said. “Future studies should focus on characterizing the optimal treatment approaches for each of these special sites.”

“This is important data,” added primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington. “We need more high-quality studies like this; we need to create long-term longitudinal data to better understand [the impact of AD on] this and other cohorts.”

TARGET-DERM is sponsored by Target RWE. Dr. Eichenfield disclosed that he has served as a consultant to or investigator for numerous pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.

Commentary by Robert Sidbury, MD, MPH

Patients with atopic dermatitis (AD) in “visible” areas such as the head, neck, and hands experience a higher impact on their quality of life than those who do not have these areas of involvement. This is a self-evident and unsurprising result but also a particularly important one to document for several reasons. First, evidence-based demonstration of quality-of-life impact is critical as we petition carriers to support the use of newer, more expensive medications. Second, from a topical therapy standpoint, we often use different medications on the head, neck, face, and hands relative to other areas. On the head and neck area we often use either weaker topical steroids to avoid side effects or nonsteroids like topical calcineurin or phosphodiesterase inhibitors; conversely, on the hands we use stronger steroids and are less likely to use nonsteroidal agents that are perceived to be less potent. These data emphasize the need to tailor therapy but ascertain whether standard approaches are satisfactory. If patients are not responding, particularly in these sensitive areas, providers should consider the outsized impact AD may be having on quality of life.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

A version of this article first appeared on Medscape.com.

This article was updated 6/10/22.

Involvement of the head, neck, face, and hands with atopic dermatitis was associated with a significantly higher impact on health-related quality of life and appeared to be associated with more severe AD, according to a large, cross-sectional study of patients with AD.

“While we know that head, neck, face, and hands seem to be significantly affected by patients with AD, there is a limited evidence basis regarding the prevalence and health-related quality of life impact of AD in these areas,” presenting author Lawrence F. Eichenfield, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium.

For the study, Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues evaluated 533 patients from the TARGET-DERM AD cohort, an ongoing, longitudinal, observational study launched in 2019 that captures patients with AD in 44 community or academic sites in the United States.

Adult, adolescent, and pediatric patients with moderate or severe Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores at enrollment were included in the analysis. The researchers used the Patient-Oriented Scoring AD (PO-SCORAD) index to gather information on involvement of the head, neck, face, hands, or other areas, and the Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index/Children’s DLQI (CDLQI) to measure health-related quality of life outcomes.

Of the 533 study participants, 453 (85%) had AD affecting the head, neck, face, hands, and other areas, while 80 (15%) had AD located in other body regions not including the head, neck, face, or hands. About 38% of all patients were using systemic treatments; most were using topical treatments.

Comorbid immune system disorders (including allergic and hypersensitivity disorders) were noted in 44.8% of patients, infections in 32.5%, asthma in 26.5%, hypertension in 18.6%, depression in 15.8%, and anxiety in 12.4%, with similar proportions observed in those with or without head, neck, face, and hand involvement.

However, patients with head, face, neck, and hand involvement, when compared with patients without those affected areas, were more likely to have severe vIGA scores (28.5% vs. 16.3%, P = .02) and a higher median total body surface area affected (15% vs. 10%, P ≤ .01). Also, while bivariable analyses did not detect statistical differences in POEM and DLQI/CDLQI by body region involvement, multivariable-adjusted models showed that patients with head, neck, face, and hand involvement were more than twice as likely to report higher DLQI/CDLQI (odds ratio, 2.09) and POEM (OR, 2.51) scores than those without head, face, neck, and hand involvement.

“These findings highlight the importance of detailed assessment of specific areas affected by AD to personalize treatment approaches to the needs of patients,” Dr. Eichenfield concluded.

Raj Chovatiya MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that the findings confirm clinical suspicions about the unique and heightened impact of facial, head/neck, and hand dermatitis. “These data show that a detailed skin examination is necessary for a complete assessment of AD,” he said. “Future studies should focus on characterizing the optimal treatment approaches for each of these special sites.”

“This is important data,” added primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington. “We need more high-quality studies like this; we need to create long-term longitudinal data to better understand [the impact of AD on] this and other cohorts.”

TARGET-DERM is sponsored by Target RWE. Dr. Eichenfield disclosed that he has served as a consultant to or investigator for numerous pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.

Commentary by Robert Sidbury, MD, MPH

Patients with atopic dermatitis (AD) in “visible” areas such as the head, neck, and hands experience a higher impact on their quality of life than those who do not have these areas of involvement. This is a self-evident and unsurprising result but also a particularly important one to document for several reasons. First, evidence-based demonstration of quality-of-life impact is critical as we petition carriers to support the use of newer, more expensive medications. Second, from a topical therapy standpoint, we often use different medications on the head, neck, face, and hands relative to other areas. On the head and neck area we often use either weaker topical steroids to avoid side effects or nonsteroids like topical calcineurin or phosphodiesterase inhibitors; conversely, on the hands we use stronger steroids and are less likely to use nonsteroidal agents that are perceived to be less potent. These data emphasize the need to tailor therapy but ascertain whether standard approaches are satisfactory. If patients are not responding, particularly in these sensitive areas, providers should consider the outsized impact AD may be having on quality of life.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

A version of this article first appeared on Medscape.com.

This article was updated 6/10/22.

Involvement of the head, neck, face, and hands with atopic dermatitis was associated with a significantly higher impact on health-related quality of life and appeared to be associated with more severe AD, according to a large, cross-sectional study of patients with AD.

“While we know that head, neck, face, and hands seem to be significantly affected by patients with AD, there is a limited evidence basis regarding the prevalence and health-related quality of life impact of AD in these areas,” presenting author Lawrence F. Eichenfield, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium.

For the study, Dr. Eichenfield, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues evaluated 533 patients from the TARGET-DERM AD cohort, an ongoing, longitudinal, observational study launched in 2019 that captures patients with AD in 44 community or academic sites in the United States.

Adult, adolescent, and pediatric patients with moderate or severe Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores at enrollment were included in the analysis. The researchers used the Patient-Oriented Scoring AD (PO-SCORAD) index to gather information on involvement of the head, neck, face, hands, or other areas, and the Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index/Children’s DLQI (CDLQI) to measure health-related quality of life outcomes.

Of the 533 study participants, 453 (85%) had AD affecting the head, neck, face, hands, and other areas, while 80 (15%) had AD located in other body regions not including the head, neck, face, or hands. About 38% of all patients were using systemic treatments; most were using topical treatments.

Comorbid immune system disorders (including allergic and hypersensitivity disorders) were noted in 44.8% of patients, infections in 32.5%, asthma in 26.5%, hypertension in 18.6%, depression in 15.8%, and anxiety in 12.4%, with similar proportions observed in those with or without head, neck, face, and hand involvement.

However, patients with head, face, neck, and hand involvement, when compared with patients without those affected areas, were more likely to have severe vIGA scores (28.5% vs. 16.3%, P = .02) and a higher median total body surface area affected (15% vs. 10%, P ≤ .01). Also, while bivariable analyses did not detect statistical differences in POEM and DLQI/CDLQI by body region involvement, multivariable-adjusted models showed that patients with head, neck, face, and hand involvement were more than twice as likely to report higher DLQI/CDLQI (odds ratio, 2.09) and POEM (OR, 2.51) scores than those without head, face, neck, and hand involvement.

“These findings highlight the importance of detailed assessment of specific areas affected by AD to personalize treatment approaches to the needs of patients,” Dr. Eichenfield concluded.

Raj Chovatiya MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that the findings confirm clinical suspicions about the unique and heightened impact of facial, head/neck, and hand dermatitis. “These data show that a detailed skin examination is necessary for a complete assessment of AD,” he said. “Future studies should focus on characterizing the optimal treatment approaches for each of these special sites.”

“This is important data,” added primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington. “We need more high-quality studies like this; we need to create long-term longitudinal data to better understand [the impact of AD on] this and other cohorts.”

TARGET-DERM is sponsored by Target RWE. Dr. Eichenfield disclosed that he has served as a consultant to or investigator for numerous pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron, and Sanofi-Genzyme. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma.

Commentary by Robert Sidbury, MD, MPH

Patients with atopic dermatitis (AD) in “visible” areas such as the head, neck, and hands experience a higher impact on their quality of life than those who do not have these areas of involvement. This is a self-evident and unsurprising result but also a particularly important one to document for several reasons. First, evidence-based demonstration of quality-of-life impact is critical as we petition carriers to support the use of newer, more expensive medications. Second, from a topical therapy standpoint, we often use different medications on the head, neck, face, and hands relative to other areas. On the head and neck area we often use either weaker topical steroids to avoid side effects or nonsteroids like topical calcineurin or phosphodiesterase inhibitors; conversely, on the hands we use stronger steroids and are less likely to use nonsteroidal agents that are perceived to be less potent. These data emphasize the need to tailor therapy but ascertain whether standard approaches are satisfactory. If patients are not responding, particularly in these sensitive areas, providers should consider the outsized impact AD may be having on quality of life.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

A version of this article first appeared on Medscape.com.

This article was updated 6/10/22.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

A version of this article first appeared on Medscape.com.

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

A version of this article first appeared on Medscape.com.

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

A version of this article first appeared on Medscape.com.

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

A version of this article first appeared on Medscape.com.

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

A version of this article first appeared on Medscape.com.

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

A version of this article first appeared on Medscape.com.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

Low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers are safe to pair with botulinum neurotoxin type A and soft-tissue fillers during the same treatment session, results from a 6-year, single-center review showed.

“These treatments can be complementary in single-session treatments and can offer increased convenience for both patients and physicians,” primary study author Jordan V. Wang, MD, MBE, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery.

To date, limited studies have demonstrated the safety of pairing botulinum neurotoxin type A and soft-tissue fillers with laser and other energy-based devices during the same treatment session on the same day, said Dr. Wang, medical research director at the Laser & Skin Surgery Center of New York. “Some concerns remain, though, regarding patient safety and efficacy,” he said. “Data on single-session treatment with low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers and either botulinum neurotoxin or fillers are lacking.”

In a retrospective review of electronic medical records conducted from May 2015 to April 2021, Dr. Wang, Roy G. Geronemus, MD, and Carolyn Kushner, MD evaluated patients who received a single-session facial treatment with either BoNT-A or soft-tissue fillers and the low-power, low-density 1,927-nm and 1,440-nm fractional diode lasers (Clear+Brilliant Perméa and Original, Solta, Pleasanton, Calif.). Safety was assessed by documenting adverse events related to the spread of BoNT-A and fillers or laser treatment of filled areas within 4 weeks.

Adverse events they looked for related to botulinum neurotoxin use included eyelid ptosis; neck weakness or spasms; impairments in chewing, swallowing, speech, and respiration; and prescriptions of apraclonidine eye drops. Filler-related adverse events they looked for included product migration, unexpected loss of filler volume, vascular occlusion, acute pain, necrosis, blindness, and burn. “For both, we looked at hospital or emergency room transfers or admissions and referrals to ENT or ophthalmology,” Dr. Wang said.

During the 6-year study period, 525 patients had 1,562 single-session laser treatments with a mean 46.4 units of BoNT-A, and 398 patients had 1,237 single-session treatments with a mean 1.6 soft-tissue filler syringes. Among those who received BoNT-A, most (93%) were female, their mean age was 51 years, and 99% were treated with a 1,927-nm wavelength at a medium setting in 87% of cases. The top five injection sites were glabella (82%), forehead (69%), periorbital area (64%), neck (40%), and jawline and/or masseters (13%).

The researchers noted one case (0.06%) where apraclonidine eye drops were prescribed for ptosis. The patient had undergone eight other single-session treatments without issue. There were no other documented adverse events directly related to spread of BoNT-A. According to Dr. Wang, this rate of ptosis is lower than the incidence with BoNT-A alone in two landmark trials studying its effects on glabellar lines, which was reported as 5.4% and 1.0%.

Among the 398 patients who received soft-tissue fillers, most (94%) were female, their mean age was 54 years, and 99% were treated with a 1927nm wavelength at a medium setting in 97% of cases. The top five injection sites were cheeks and/or tear troughs (89%), perioral area and/or marionette lines (77%), lips (34%), nasolabial folds (19%), and temples (11%), and the mean number of filler syringes per treatment was 1.6. Slightly more than half (51%) had 1 session, while the remainder had 2 to greater than 10 sessions. The researchers observed no documented adverse events related to spread of fillers or laser treatment of filled areas.

“This laser is a low-powered device that creates small, superficial, and transient microchannels, which likely contributes to the safety of single-session treatments with cosmetic injectables,” Dr. Wang said. However, prospective studies are needed to further validate these results, he added.

“With this very mild laser, it is not surprising that combined treatment had no effect,” said Eric F. Bernstein, MD, MSE, director of the Main Line Center for Laser Surgery in Ardmore, Pa., who was asked to comment on the study results. “There have been numerous anecdotal reports of spreading of botulinum toxin effect to areas not in the target area for treatment following a variety of lasers, including the more powerful version of the laser used in this study. In addition, spread following vascular and other lasers has been reported,” he noted

The laser used in this study, Dr. Bernstein continued, “is low powered and emits a wavelength that is very superficially absorbed, resulting in injury to the stratum corneum, superficial epidermis, or possibly the very superficial dermis, and is often used by physician extenders and not physicians – although I suspect this is not the case in the current study. One can have a reasonable degree of confidence when combining this laser with injectables, but these results cannot be extrapolated to other devices.”

The abstract received the annual ASDS Carruthers Award during the meeting. Dr. Wang reported that he is a consultant or advisor to Allergan, Alastin, AVAVA, Cynosure, Lutronic, Novoxel, Sofwave, and Solta. Dr. Bernstein reported having received research funding from Cynosure, Candela, and Acclaro. He also has received consulting fees from Cynosure and holds ownership interest in Candela, Novoxel, OnSite, Joylux, and Acclaro and has served on the advisory board for Novoxel, Cynosure, and Acclaro.

Many health care professionals do not feel prepared to cope with a patient overdose death or to support a colleague after such a death, new research suggests.

However, results from a survey study also showed that colleagues were an important source of support in the wake of this type of event.

“A patient overdose death can change clinical decision-making for providers experiencing high levels of stress related to the overdose death,” noted the investigators, led by Amy Yule, MD, director of adolescent addiction psychiatry, Boston Medical Center, and assistant professor of psychiatry at Boston University Medical Center.

The findings were presented by Dr. Yule at the annual meeting of the American Academy of Addiction Psychiatry.
 

All-time high

As reported by this news organization, there has recently been a record number of drug overdose deaths. And these deaths affect families, communities, and often providers, Dr. Yule told meeting attendees.

Previous research has looked at the impact of drug overdose deaths and the opioid epidemic on first responders and community health workers in the field of overdose prevention.

“But there’s less in the literature to my knowledge that describes the experience of providers and clinicians who are working in more formalized medical settings,” said Dr. Yule.

In December 2020, researchers sent an email to members of the Providers Clinical Support System (PCSS) inviting them to complete an anonymous survey. The PCSS program was created in response to the opioid overdose epidemic to train primary care clinicians in the prevention and treatment of opioid use disorders.

A total of 12,204 members received the email, 1,064 opened the survey link, and 523 completed the survey.

Participants were mostly White and female, with an average age of 52 years. Respondents had been practicing for an average of about 16 years.

The largest responder group was physicians (47%), followed by counselors (29%), nurse practitioners (17%), and nurses (7%).

Among physician respondents, 41% reported having received additional formal training in addiction.

Only 24% of the respondents indicated they received training in “postvention,” which refers to interventions after a suicide to support the bereaved. Such interventions “could be helpful in potentially preparing them for a drug overdose death in their practice,” said Dr. Yule.
 

Categories of preparedness

The survey inquired about three categories of preparedness: coping with a drug overdose death, providing support to a colleague, and talking with families who have lost a member to a drug overdose.

Overall, 59% said they felt somewhat or fairly well prepared for the first two categories and 55% for the third category.

“I think it’s notable that there is a higher percentage of people who felt not at all prepared to talk with family members (20.5%), compared to those who felt not at all prepared to cope with a drug overdose death (13.8%) or prepared to support a colleague (12%),” Dr. Yule said.

More than half of respondents (55%) indicated a drug overdose death had occurred in their own practice.

The survey also looked at frequency of consultations with colleagues, critical incident debriefing sessions, and interactions with a patient’s family.

Almost half (48%) of the sample said they consulted with a colleague after most patient overdose deaths. Only 24% said they had a critical incidence debriefing session after most of these events, and 20% said they interacted with the patient’s family.

Asked what resources they found helpful for coping with a recent patient drug overdose death, respondents flagged their colleagues and meetings with families.

The survey also examined provider trauma after a patient drug overdose death, using the Impact of Event Scale–R. “If the score is above a certain cutoff level, there is potential concern” for PTSD, Dr. Yule said.

Among the 141 respondents who had a patient drug overdose death in their practice during the previous year, 121 completed this trauma scale. Of these, 18% had “a very elevated” score, Dr. Yule reported.
 

Sources of support

Commenting on the survey study, Larissa Mooney, MD, associate professor and director of the addiction psychiatry division in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said it is not surprising that many providers do not feel adequately prepared to cope with an overdose death, or how to support a colleague after such an event.

“This is not routinely covered in training, and patient overdose may occur without warning signs,” said Dr. Mooney, who was not involved with the research.

However, these new findings suggest a range of potential sources of support for providers after a patient overdose death that may be helpful, “including colleagues, friends, therapy, supervision, and meeting with the patient’s family,” she said.

The study received funding from the PCSS. Dr. Yule disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Many health care professionals do not feel prepared to cope with a patient overdose death or to support a colleague after such a death, new research suggests.

However, results from a survey study also showed that colleagues were an important source of support in the wake of this type of event.

“A patient overdose death can change clinical decision-making for providers experiencing high levels of stress related to the overdose death,” noted the investigators, led by Amy Yule, MD, director of adolescent addiction psychiatry, Boston Medical Center, and assistant professor of psychiatry at Boston University Medical Center.

The findings were presented by Dr. Yule at the annual meeting of the American Academy of Addiction Psychiatry.
 

All-time high

As reported by this news organization, there has recently been a record number of drug overdose deaths. And these deaths affect families, communities, and often providers, Dr. Yule told meeting attendees.

Previous research has looked at the impact of drug overdose deaths and the opioid epidemic on first responders and community health workers in the field of overdose prevention.

“But there’s less in the literature to my knowledge that describes the experience of providers and clinicians who are working in more formalized medical settings,” said Dr. Yule.

In December 2020, researchers sent an email to members of the Providers Clinical Support System (PCSS) inviting them to complete an anonymous survey. The PCSS program was created in response to the opioid overdose epidemic to train primary care clinicians in the prevention and treatment of opioid use disorders.

A total of 12,204 members received the email, 1,064 opened the survey link, and 523 completed the survey.

Participants were mostly White and female, with an average age of 52 years. Respondents had been practicing for an average of about 16 years.

The largest responder group was physicians (47%), followed by counselors (29%), nurse practitioners (17%), and nurses (7%).

Among physician respondents, 41% reported having received additional formal training in addiction.

Only 24% of the respondents indicated they received training in “postvention,” which refers to interventions after a suicide to support the bereaved. Such interventions “could be helpful in potentially preparing them for a drug overdose death in their practice,” said Dr. Yule.
 

Categories of preparedness

The survey inquired about three categories of preparedness: coping with a drug overdose death, providing support to a colleague, and talking with families who have lost a member to a drug overdose.

Overall, 59% said they felt somewhat or fairly well prepared for the first two categories and 55% for the third category.

“I think it’s notable that there is a higher percentage of people who felt not at all prepared to talk with family members (20.5%), compared to those who felt not at all prepared to cope with a drug overdose death (13.8%) or prepared to support a colleague (12%),” Dr. Yule said.

More than half of respondents (55%) indicated a drug overdose death had occurred in their own practice.

The survey also looked at frequency of consultations with colleagues, critical incident debriefing sessions, and interactions with a patient’s family.

Almost half (48%) of the sample said they consulted with a colleague after most patient overdose deaths. Only 24% said they had a critical incidence debriefing session after most of these events, and 20% said they interacted with the patient’s family.

Asked what resources they found helpful for coping with a recent patient drug overdose death, respondents flagged their colleagues and meetings with families.

The survey also examined provider trauma after a patient drug overdose death, using the Impact of Event Scale–R. “If the score is above a certain cutoff level, there is potential concern” for PTSD, Dr. Yule said.

Among the 141 respondents who had a patient drug overdose death in their practice during the previous year, 121 completed this trauma scale. Of these, 18% had “a very elevated” score, Dr. Yule reported.
 

Sources of support

Commenting on the survey study, Larissa Mooney, MD, associate professor and director of the addiction psychiatry division in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said it is not surprising that many providers do not feel adequately prepared to cope with an overdose death, or how to support a colleague after such an event.

“This is not routinely covered in training, and patient overdose may occur without warning signs,” said Dr. Mooney, who was not involved with the research.

However, these new findings suggest a range of potential sources of support for providers after a patient overdose death that may be helpful, “including colleagues, friends, therapy, supervision, and meeting with the patient’s family,” she said.

The study received funding from the PCSS. Dr. Yule disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Many health care professionals do not feel prepared to cope with a patient overdose death or to support a colleague after such a death, new research suggests.

However, results from a survey study also showed that colleagues were an important source of support in the wake of this type of event.

“A patient overdose death can change clinical decision-making for providers experiencing high levels of stress related to the overdose death,” noted the investigators, led by Amy Yule, MD, director of adolescent addiction psychiatry, Boston Medical Center, and assistant professor of psychiatry at Boston University Medical Center.

The findings were presented by Dr. Yule at the annual meeting of the American Academy of Addiction Psychiatry.
 

All-time high

As reported by this news organization, there has recently been a record number of drug overdose deaths. And these deaths affect families, communities, and often providers, Dr. Yule told meeting attendees.

Previous research has looked at the impact of drug overdose deaths and the opioid epidemic on first responders and community health workers in the field of overdose prevention.

“But there’s less in the literature to my knowledge that describes the experience of providers and clinicians who are working in more formalized medical settings,” said Dr. Yule.

In December 2020, researchers sent an email to members of the Providers Clinical Support System (PCSS) inviting them to complete an anonymous survey. The PCSS program was created in response to the opioid overdose epidemic to train primary care clinicians in the prevention and treatment of opioid use disorders.

A total of 12,204 members received the email, 1,064 opened the survey link, and 523 completed the survey.

Participants were mostly White and female, with an average age of 52 years. Respondents had been practicing for an average of about 16 years.

The largest responder group was physicians (47%), followed by counselors (29%), nurse practitioners (17%), and nurses (7%).

Among physician respondents, 41% reported having received additional formal training in addiction.

Only 24% of the respondents indicated they received training in “postvention,” which refers to interventions after a suicide to support the bereaved. Such interventions “could be helpful in potentially preparing them for a drug overdose death in their practice,” said Dr. Yule.
 

Categories of preparedness

The survey inquired about three categories of preparedness: coping with a drug overdose death, providing support to a colleague, and talking with families who have lost a member to a drug overdose.

Overall, 59% said they felt somewhat or fairly well prepared for the first two categories and 55% for the third category.

“I think it’s notable that there is a higher percentage of people who felt not at all prepared to talk with family members (20.5%), compared to those who felt not at all prepared to cope with a drug overdose death (13.8%) or prepared to support a colleague (12%),” Dr. Yule said.

More than half of respondents (55%) indicated a drug overdose death had occurred in their own practice.

The survey also looked at frequency of consultations with colleagues, critical incident debriefing sessions, and interactions with a patient’s family.

Almost half (48%) of the sample said they consulted with a colleague after most patient overdose deaths. Only 24% said they had a critical incidence debriefing session after most of these events, and 20% said they interacted with the patient’s family.

Asked what resources they found helpful for coping with a recent patient drug overdose death, respondents flagged their colleagues and meetings with families.

The survey also examined provider trauma after a patient drug overdose death, using the Impact of Event Scale–R. “If the score is above a certain cutoff level, there is potential concern” for PTSD, Dr. Yule said.

Among the 141 respondents who had a patient drug overdose death in their practice during the previous year, 121 completed this trauma scale. Of these, 18% had “a very elevated” score, Dr. Yule reported.
 

Sources of support

Commenting on the survey study, Larissa Mooney, MD, associate professor and director of the addiction psychiatry division in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said it is not surprising that many providers do not feel adequately prepared to cope with an overdose death, or how to support a colleague after such an event.

“This is not routinely covered in training, and patient overdose may occur without warning signs,” said Dr. Mooney, who was not involved with the research.

However, these new findings suggest a range of potential sources of support for providers after a patient overdose death that may be helpful, “including colleagues, friends, therapy, supervision, and meeting with the patient’s family,” she said.

The study received funding from the PCSS. Dr. Yule disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Use of vascular lasers in the Medicare population is increasing, primarily among dermatologists. In addition, as a proportion of Medicare charges submitted that were reimbursed, the highest reimbursements were for dermatologists and those in the Western geographic region.

Those are among the key findings from an analysis that aimed to characterize trends in use and reimbursement patterns of vascular lasers in the Medicare-insured population.

“There are several modalities for vascular laser treatment, including the pulse dye laser, the frequency doubled KTP laser, and others,” presenting author Partik Singh, MD, MBA, said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “Laser treatment of vascular lesions may sometimes be covered by insurance, depending on the indication, but little is known about how and which clinicians are taking advantage of this covered treatment.”

Dr. Singh, a 2nd-year dermatology resident at the University of Rochester Medical Center, and coauthor Mara Weinstein Velez, MD, extracted data from the 2012-2018 Medicare Public Use File, which includes 100% fee-for-service, non–Medicare Advantage claims based on CPT codes, yet no information on patient data, clinical context, or indications. Outcomes of interest were total vascular laser claims per year, annual vascular laser claims per clinician, annual clinicians using vascular lasers, accepted reimbursements defined by the allowed charge or the submitted charge to Medicare, and clinical specialties and geographic location.

The researchers found that more than half of clinicians who used vascular lasers during the study period were dermatologists (55%), followed by general surgeons (6%), family practice/internal medicine physicians (5% each) and various others. Use of vascular lasers among all clinicians increased 10.5% annually during the study period, from 3,786 to 6,883, and was most pronounced among dermatologists, whose use increased 18.4% annually, from 1,878 to 5,182. “Nondermatologists did not have a big change in their overall utilization rate, but they did have a steady utilization of vascular lasers, roughly at almost 2,000 claims per year,” Dr. Singh said.

The researchers also observed that the use of vascular lasers on a per-clinician basis increased 7.4% annually among all clinicians during the study period, from 77.3 to 118.7. This was mostly driven by dermatologists, whose per-clinician use increased 10.4% annually, from 81.7 to 148.7. Use by nondermatologists remained about stable, with just a 0.1% increase annually, from 73.4 to 74. In addition, the number of clinicians who billed for vascular laser procedures increased 2.9% annually between 2012 and 2018, from 49 to 58. This growth was driven mostly by dermatologists, who increased their billing for vascular laser procedures by 7.2% annually, from 23 to 35 clinicians.

In other findings, dermatologists were reimbursed at 68.3% of submitted charges, compared with 59.3% of charges submitted by other clinicians (P = .0001), and reimbursement rates were greatest in the Western geographic region of the United States vs. the Northeast, Midwest, and Southern regions (73.1% vs. 50.2%, 65.4%, and 55.3%, respectively; P < .0001).

“Use of vascular lasers is increasing primarily among dermatologists, though there is steady use of these procedures by nondermatologists,” Dr. Singh concluded. “Medicare charges were more often fully reimbursed when billed by dermatologists and those in the Western U.S., perhaps suggesting a better familiarity with appropriate indications and better administrative resources for coverage of vascular laser procedures.”

After the meeting, Dr. Singh acknowledged certain limitations of the analysis, including the fact that it “was limited only to Medicare Part B fee-for-service claims, not including Medicare Advantage,” he told this news organization. “Our conclusions do not necessarily hold true for Medicaid or commercial insurers, for instance. Moreover, this dataset doesn’t provide patient-specific information, such as the indication for the procedure. Further studies are needed to characterize utilization of various lasers in not only Medicare beneficiaries, but also those with Medicaid, private insurance, and patients paying out-of-pocket. Additionally, study is also needed to explain why these differences in reimbursement hold true.”

The researchers reported having no relevant financial disclosures.

dbrunk@mdedge.com

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

aotto@mdedge.com

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

aotto@mdedge.com

Remarkable results were reported at the annual meeting of the American Society of Hematology for the investigational drug fitusiran to prevent bleeding in hemophilia patients.

Fitusiran is a small interfering RNA molecule that blocks antithrombin production in liver cells. Instead of taking the traditional approach in hemophilia treatment of boosting the coagulation cascade by replacing what’s missing, the idea of fitusiran is to short circuit the body’s anticoagulation system by targeting antithrombin.

Patients in two trials presented at the meeting, ATLAS-A/B and ATLAS-INH, had about a 90% reduction in their annualized bleeding rates when treated with prophylactic fitusiran, with half or more having no bleeds that required treatment during the 9-month trials. The median annualized bleeding rate fell to 0, trial investigators reported at the meeting.

These findings held in both hemophilia A and B with and without inhibitors, which are antibodies formed against exogenous clotting factors, and on subanalysis of spontaneous and joint bleeding rates. Reduced bleeding was associated with substantial improvements in health-care related quality of life, particularly in the physical health domain.
 

A question about study design

An audience member at ASH noted that the trials didn’t compare fitusiran against prophylactic treatment, which is standard of care for hemophilia, but rather against episodic treatment – concentrated factors or bypassing agents in subjects with inhibitors – once subjects in the control groups started to bleed.

Still, the numbers reported in the studies “have never been achieved with standard prophylaxis in the past.” Furthermore, standard prophylaxis requires lifelong intravenous infusions, sometimes several a week, said lead ATLAS-A/B investigator Alok Srivastava, MD, a hematologist at the Christian Medical College in Vellore, India.

Fitusiran was dosed in the studies as a once-a-month 80 mg subcutaneous injection, so is much less bothersome. Also, it seems likely that some patients will only need dosing every other month. Maker Sanofi Genzyme is exploring lower and less frequent dosing to reduce thrombotic event risks that emerged in earlier studies, said Steven Pipe, MD, a pediatric hematologist at the University of Michigan, Ann Arbor, and the senior investigator on ATLAS-A/B, which assessed fitusiran in patients without inhibitors.

Serious thrombotic events occurred in two fitusiran patients in the trials, one of which led to discontinuation.
 

No pricing information

Overall, “I think [fitusiran] is a tremendous leap forward” with “the opportunity to transform the day-to-day lives of patients,” particularly those with hemophilia B, who have limited treatment options, Dr. Pipe said.

If approved for the U.S. market, fitusiran will go up against the monoclonal antibody emicizumab (Hemlibra), a subcutaneous injection dosed weekly to monthly that mimics the function of factor VIII, so it’s approved only for hemophilia A with or without inhibitors.

Several audience members at ASH noted that a major consideration for fitusiran, if approved, will be its cost. There’s no pricing information yet, but annual list price for emicizumab is reported to be in the $500,000 range.

For hemophilia A, “it will come to what proves to be the most efficacious and safe, with also consideration given to pricing,” Nigel Key, MD, a hematologist at the University of North Carolina at Chapel Hill, said in a comment.
 

Trial details

In ATLAS-A/B, 80 male patients were randomized to prophylactic fitusiran once monthly and 40 to continue with clotting factors as needed for bleeding. Just over 20% had hemophilia B, the rest hemophilia A. The mean age was 34 years, and subjects had a mean of about 12 bleeds in the 6 months leading up to the study.

Half of the fitusiran group had no treated bleeds during the study period versus only 5% in the control arm.

The five treatment emergent serious adverse events in the fitusiran arm included cholelithiasis in two subjects, plus cholecystitis, lower respiratory tract infection, and asthma in one each. Two fitusiran patients discontinued treatment because of cholecystitis and increased alanine aminotransferase.

ATLAS-INH had the same study design, and investigated patients with inhibitors; again, just over 20% had hemophilia B, the rest A. Mean age was 28 years, and patients had a mean of about 13 bleeds over the 6 months before the study. A total of 38 subjects were randomized to fitusiran, and 19 to bypassing agents as needed.

Almost 66% of fitusiran patients had no treated bleeds versus about 5% in the control arm.

none provided

There “was far less bleeding both for hemophilia A and B. It’s definitely a clinically meaningful and important” effect, said ATLAS-INH lead investigator Guy Young, MD, director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles.

He said the improved quality of life with fitusiran noted in both trials was “not surprising. If you only have to dose once a month subcutaneously, and you are not bleeding, of course your quality of life is going to improve.”

Both fitusiran thrombotic events occurred in ATLAS-INH. One patient developed deep vein thrombosis, subclavian vein thrombosis, and superficial thrombophlebitis but stayed in the study. Another discontinued after developing suspected spinal vessel thrombosis. Serious adverse events among five other subjects included acute cholecystitis and hematuria.

Fitusiran was associated with liver enzyme elevations in both trials, but they were generally mild to moderate.

The studies were funded by fitusiran maker Sanofi Genzyme. Several investigators were employees. Dr. Pipe is a consultant, Dr. Srivastava is a researcher and adviser, and Dr. Young is a speaker and consultant for the company and disclosed honoraria from it. Dr. Key had no relevant disclosures.

aotto@mdedge.com